Treatment of hypokalemia with amiloride unmasked hypercalcemia and hyperparathyroidism: A case report.

Colonic pseudo-obstruction, also called Ogilvie's syndrome, occurs due to impaired intestinal propulsion, and may be caused by electrolyte imbalances such as hypokalemia and some endocrine disorders such as hyperparathyroidism. Secretory diarrhea due to intestinal pseudo-obstruction can cause hypokalemia. Diuretics such as amiloride can be used to treat hypokalemia, however in this case, treatment with amiloride induced hypercalcemia and unmasked hyperparathyroidism. A 73-year-old female with a history of hypertension and parathyroid adenoma presented with recurrent colonic pseudo-obstruction and chronic hypokalemia. Her hypokalemia was treated with amiloride, causing hypercalcemia of 14.4 mg/dL, elevated PTH, and altered mental status. Amiloride was subsequently discontinued with improvement in her symptoms, and her hyperparathyroidism was treated with cinacalcet. To our knowledge, this is the first report of amiloride unmasking hyperparathyroidism and inducing hypercalcemia.

Neuroendocrine tumors in a patient with multiple endocrine neoplasia type 1 syndrome: A case report and review of the literature.

RATIONALE: Hyperparathyroidism is caused by parathyroid tumors combined with gastroenteropancreatic tumors and pituitary tumors, which is common in patients with multiple endocrine neoplasia 1 syndrome (MEN-1). As its main pathogenic factor involves genetic mutations, it can cause a variety of different clinical symptoms. However, cases with negative genetic testing results and multiple nonfunctional malignant neuroendocrine tumors (NETs) with metastasis are relatively rare. PATIENT CONCERNS: A 33-year-old man was admitted to the hospital for hyperparathyroidism. Imaging examination revealed multiple nodules in the parathyroid gland, pancreas, thymus, and adrenal gland, and multiple metastases to the lung, liver, thoracolumbar, as well as mediastinal lymph nodes. DIAGNOSES: After multidisciplinary consultation, this patient was diagnosed with MEN-1 syndrome with various original tumors and multiple systemic metastases. INTERVENTIONS: The patient underwent parathyroid tumor resection and metastasis biopsy. OUTCOMES: The patient received denosumab and sorafenib treatment. LESSONS: As an autosomal dominant hereditary disease, MEN-1 patients present with parathyroid hyperplasia, pancreatic and intestinal tumors, pituitary tumors, and so on, which are caused by genetic mutations. These patients would have hyperparathyroidism, hypoglycemia, gastric ulcer, and gastrointestinal diseases. However, some patients with MEN-1 syndrome cannot be diagnosed by genetic testing and simultaneously present with multiple nonfunctional NETs with systemic metastasis. This increases the difficulty of diagnosis and the subsequent treatment.

A Diagnostic Journey.

We describe the case of a patient who came with features suggestive of diabetic ketoacidosis. On further evaluation of DKA, we found that it was caused by acute pancreatitis. This acute pancreatitis was found to be caused by hypercalcemia, which was in turn due to primary hyperparathyroidism. Imaging studies done for hyperparathyroidism revealed a thyroid nodule which later turned out to be malignant. This patient was also incidentally found to have hypertrophic obstructive cardiomyopathy.

Missed Opportunities to Diagnose and Treat Tertiary Hyperparathyroidism After Transplant.

INTRODUCTION: Tertiary hyperparathyroidism (3HPT) is common after renal transplant. However, guidelines for diagnosis are not clear and few patients are treated surgically. This study aims to determine rates of diagnosis and treatment of 3HPT in renal transplant patients with hypercalcemia. MATERIALS AND METHODS: This retrospective chart review identified all renal transplant recipients at a single tertiary care institution between 2011 and 2021. Patients with post-transplant hypercalcemia (> 10.2 mg/dL) were identified. The time in months of index hypercalcemia was noted. Measurement of parathyroid hormone (PTH) levels after index hypercalcemia was determined and noted as elevated if > 64 pg/mL at least 6 mo after transplant. Documentation of symptoms of hyperparathyroidism, a diagnosis of hyperparathyroidism in the electronic medical record, and medical or surgical management of patients with classic 3HPT (elevated calcium and PTH) were determined. RESULTS: Of 383 renal transplant recipients, hypercalcemia was identified in 132 patients. The majority of hypercalcemic patients had PTH levels measured (127, 96.2%). PTH was elevated in 109 (82.6%). Among the 109 patients with classic 3HPT, 54 (49.5%) had a documented diagnosis of hyperparathyroidism in the electronic medical record (P = 0.01). Kidney stones or abnormal DEXA scan were present in 16 (14.7%) and 18 (16.5%), respectively. Most patients were managed non-surgically (101, 92.6%); calcimimetics were prescribed for 42 (38.5%, P = 0.01). Eight (7.3%) patients with classic 3HPT were referred to a surgeon (P = 0.35); all were initially prescribed calcimimetics (P = 0.001). CONCLUSIONS: 3HPT is underdiagnosed in patients with elevated calcium and PTH levels post-transplant. A significant percentage of these patients go without surgical referral and curative treatment.

A two-generation hyperparathyroidism-jaw tumor (HPT-JT) syndrome family: clinical presentations, pathological characteristics and genetic analysis: a case report.

BACKGROUND: Hyperparathyroidism-Jaw Tumor (HPT-JT) is caused by inactivating germline mutations of CDC73. This hereditary disease can present with a range of symptoms. Jaw ossifying fibroma (OF) is one of the most important clinical presentations, affecting 30% of HPT-JT patients. However, OF is easily confused with other fibro-osseous lesions (FOLs) of the jaw. The correct diagnosis of HPT-JT is a real challenge and must be confirmed by genetic testing. CASE PRESENTATION: A female proband and her father suffered from multiple and recurrent FOLs in the jaw. Considering well demarcated margin and heterogeneous calcified substance lying in a variable density of fibrous stroma, we reached the diagnosis of jaw OF through radiologic and microscopic analyses. Additionally, the proband presented with chronic anemia resulting from menorrhagia, as well as renal mixed epithelial and stromal tumor (MEST). Two patients both presented with no evidence of Hyperparathyroidism (HPT). A germline start codon mutation (c.1A > G) of CDC73 was identified in them. Copy number loss at the CDC73 gene locus was verified in the jaw tumor sample of the proband. CONCLUSION: Regardless of whether HPT manifestations are present, patients with heritable jaw OF may be at risk for HPT-JT. Genetic testing should be adopted to confirm the diagnosis. Early recognition of HPT-JT helps to better develop tailored treatment plans and surveillance programs.

[Hypercalcemia - Diagnosis and Management]. / Hyperkalzämie ­ Diagnose, Abklärung und Therapie.

Hypercalcemia - Diagnosis and Management Abstract. The diagnostic workup of hypercalcemia requires a thorough patient history, a focused clinical examination as well as a step-by-step laboratory diagnostic approach. In order to detect the exact aetiology of hypercalcemia an accurate measurement of serum calcium in correlation with the parathyroid hormone level is therefore essential. Primary hyperparathyroidism and malignancy-related hypercalcemia are responsible for about 90% of all hypercalcemia cases. Therefore, these two pathologies should always be considered in the diagnostic approach. The therapeutic procedure is based on the aetiology and severity of the hypercalcemia.

Machine Learning-Derived Integer-Based Score and Prediction of Tertiary Hyperparathyroidism among Kidney Transplant Recipients: An Integer-Based Score to Predict Tertiary Hyperparathyroidism.

BACKGROUND AND OBJECTIVES: Tertiary hyperparathyroidism in kidney allograft recipients is associated with bone loss, allograft dysfunction, and cardiovascular mortality. Accurate pretransplant risk prediction of tertiary hyperparathyroidism may support individualized treatment decisions. We aimed to develop an integer score system that predicts the risk of tertiary hyperparathyroidism using machine learning algorithms. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used two separate cohorts: a derivation cohort with the data of kidney allograft recipients (n=669) who underwent kidney transplantation at Severance Hospital, Seoul, Korea between January 2009 and December 2015 and a multicenter registry dataset (the Korean Cohort Study for Outcome in Patients with Kidney Transplantation) as an external validation cohort (n=542). Tertiary hyperparathyroidism was defined as post-transplant parathyroidectomy. The derivation cohort was split into 75% training set (n=501) and 25% holdout test set (n=168) to develop prediction models and integer-based score. RESULTS: Tertiary hyperparathyroidism requiring parathyroidectomy occurred in 5% and 2% of the derivation and validation cohorts, respectively. Three top predictors (dialysis duration, pretransplant intact parathyroid hormone, and serum calcium level measured at the time of admission for kidney transplantation) were identified to create an integer score system (dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level [DPC] score; 0-15 points) to predict tertiary hyperparathyroidism. The median DPC score was higher in participants with post-transplant parathyroidectomy than in those without (13 versus three in derivation; 13 versus four in external validation; P<0.001 for all). Pretransplant dialysis duration, pretransplant serum parathyroid hormone level, and pretransplant calcium level score predicted post-transplant parathyroidectomy with comparable performance with the best-performing machine learning model in the test set (area under the receiver operating characteristic curve: 0.94 versus 0.92; area under the precision-recall curve: 0.52 versus 0.47). Serial measurement of DPC scores (≥13 at least two or more times, 3-month interval) during 12 months prior to kidney transplantation improved risk classification for post-transplant parathyroidectomy compared with single-time measurement (net reclassification improvement, 0.28; 95% confidence interval, 0.02 to 0.54; P=0.03). CONCLUSIONS: A simple integer-based score predicted the risk of tertiary hyperparathyroidism in kidney allograft recipients, with improved classification by serial measurement compared with single-time measurement. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER: Korean Cohort Study for Outcome in Patients with Kidney Transplantation (KNOW-KT), NCT02042963 PODCAST: This article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2022_06_10_CJN15921221.mp3.

Transient neonatal hypocalcaemia caused by maternal hyperparathyroidism.

Hypocalcaemia in neonates can range from asymptomatic to a potentially life-threatening condition. We present a case of a 36 weeks gestational age boy, admitted to our neonatal intensive care unit for jitteriness, mild hypotonia and breastfeeding difficulties. By the ninth day of life, he presented with late-onset hypocalcaemia, hypomagnesaemia, low 25-OH-vitamin D and inappropriately normal parathyroid hormone. Further investigation revealed maternal hypercalcaemia with high parathyroid hormone. Maternal asymptomatic hyperparathyroidism was diagnosed and admitted as the cause of neonatal hypocalcaemia. There was a clinical improvement and calcium levels stabilisation after treatment with calcium gluconate and vitamin D3 This case highlights the importance of careful evaluation of neonatal late-onset hypocalcaemia in uncovering asymptomatic maternal hyperparathyroidism.

Manifestations of hyperparathyroidism in the jaws: Concepts, mechanisms, and clinical aspects.

Hyperparathyroidism is one of the most common endocrine disorders worldwide. In countries where routine biochemical screening is not common, symptomatic hyperparathyroidism predominates. Its manifestations include skeletal alterations, calcification of soft tissues, kidney stones, and functional alterations in other systems. Notably, jaw alterations can be the first clinical sign of hyperparathyroidism, including brown tumor, renal osteodystrophy, osteitis fibrosa, and leontiasis ossea, and knowing such conditions is of core importance for the multidisciplinary diagnosis and management of hyperparathyroidism. We aimed to perform a concise review, systematizing the concepts and mechanisms underlying hyperparathyroidism and associated gnathic alterations. In addition, a detailed description of the clinical aspects of the jaw manifestations is presented.

Diagnosis and localization of parathyroid adenomas using 16-slice SPECT/CT: A clinicopathological correlation.

INTRODUCTION: This study aimed to evaluate a new 16-slice SPECT/CT scanner at Auckland City Hospital for its use in the detection and localization of parathyroid adenomas in patients with primary, secondary and tertiary hyperparathyroidism. The secondary outcome was to compare findings from SPECT/CT with ultrasound and operative findings. METHODS: One hundred patients who underwent a SPECT/CT scan for primary/secondary/tertiary hyperparathyroidism were included in this study. Of these patients, 45 received surgery. SPECT/CT and ultrasound findings were collated for each patient, and of those who received surgery, operative and pathological findings were compared with those on SPECT/CT. RESULTS: The sensitivity of diagnosis and localization was 86.5% (95% CI: 71.2-95.5%). Specificity was 25.0% (95% CI: 3.2-65.1%). Comparison between SPECT/CT and ultrasound findings demonstrated a kappa coefficient of 0.203 (95% CI: -0.036 to 0.442), correlating with fair agreement. These figures are in line with other published series. CONCLUSION: The SPECT/CT scanner (and associated reporters) at Auckland City Hospital demonstrates high sensitivity in the detection and localization of parathyroid adenomas and is an effective first-line investigation in patients with primary/secondary/tertiary hyperparathyroidism.

Prevalence and risk factors for tertiary hyperparathyroidism in kidney transplant recipients.

BACKGROUND: Tertiary hyperparathyroidism after kidney transplantation has been associated with graft dysfunction, cardiovascular morbidity, and osteopenia; however, its true prevalence is unclear. The objective of our study was to evaluate the prevalence of and risk factors for tertiary hyperparathyroidism. METHODS: A prospective cohort of 849 adult kidney transplantation recipients (December 2008-February 2020) was used to estimate the prevalence of hyperparathyroidism 1-year post-kidney transplant. Tertiary hyperparathyroidism was defined as hypercalcemia (≥10mg/dL) and hyperparathyroidism (parathyroid hormone≥70pg/mL) 1-year post-kidney transplantation. Modified Poisson regression models were used to evaluate risk factors associated with the development of both persistent hyperparathyroidism and tertiary hyperparathyroidism. RESULTS: Among kidney transplantation recipients, 524 (61.7%) had persistent hyperparathyroidism and 182 (21.5%) had tertiary hyperparathyroidism at 1-year post-kidney transplantation. Calcimimetic use before kidney transplantation was associated with 1.30-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.30, 95% CI: 1.12-1.51) and 1.84-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 1.84, 95% CI: 1.25-2.72). Pre-kidney transplantation parathyroid hormone ≥300 pg/mL was associated with 1.49-fold higher risk of persistent hyperparathyroidism (adjusted prevalence ratio = 1.49, 95% CI = 1.19-1.85) and 2.21-fold higher risk of tertiary hyperparathyroidism (adjusted prevalence ratio = 2.21, 95% CI = 1.25-3.90). Pre-kidney transplantation tertiary hyperparathyroidism was associated with an increased risk of post-kidney transplantation tertiary hyperparathyroidism (adjusted prevalence ratio = 1.71, 95% CI = 1.29-2.27), but not persistent hyperparathyroidism. Furthermore, 73.0% of patients with persistent hyperparathyroidism and 61.5% with tertiary hyperparathyroidism did not receive any treatment at 1-year post-kidney transplantation. CONCLUSION: Persistent hyperparathyroidism affected 61.7% and tertiary hyperparathyroidism affected 21.5% of kidney transplantation recipients; however, the majority of patients were not treated. Pre-kidney transplantation parathyroid hormone levels ≥300pg/mL and the use of calcimimetics are associated with the development of tertiary hyperparathyroidism. These findings encourage the re-evaluation of recommended pre-kidney transplantation parathyroid hormone thresholds and reconsideration of pre-kidney transplantation secondary hyperparathyroidism treatments to avoid the adverse sequelae of tertiary hyperparathyroidism in kidney transplantation recipients.

New-Onset Hypercalcemia After Renal Transplant: An Infectious Etiology Beyond Persistent Hyperparathyroidism.

Pneumocystis jirovecii pneumonia is an opportunistic infection in kidney transplant recipients. It may be complicated by hypercalcemia. Here, we discuss a 59-year-old man who presented with respiratory symptoms and hypercalcemia. He had undergone a deceased donor kidney transplant 2 years previously. The patient had persistent hyperparathyroidism, but his serum calcium level was normal. At the time of admission, his serum calcium level had increased and his parathyroid hormone level was suppressed. He was diagnosed with Pneumocystis jirovecii pneumonia. Serum calcium and parathyroid hormone levels returned to baseline values after treatment. Pneumocystis jirovecii pneumonia is an important infection that can present with hypercalcemia among kidney transplant recipients.

A neonate with late-onset hypocalcemia due to unrecognized maternal hyperparathyroidism and a systematic overview of similar cases.

Objective: Neonatal seizures are alarming manifestations of an underlying significant disorder demanding immediate attention and intervention. Hypocalcemia, although rare, must be considered in the differential diagnosis of neonatal seizures. Method: We present an unusual case of a 10-day-old infant with unexplained symptomatic hypocalcemia, experiencing multiple episodes of focal tonic-clonic seizures, born by an entirely asymptomatic mother. Moreover, we conducted a systematic search in PubMed and Scopus databases to present a clinical overview of all similar cases. Result: Maternal laboratory investigation revealed markedly increased calcium levels with concomitant high parathyroid hormone levels due to a parathyroid adenoma, undiagnosed during antenatal checkup. Conclusion: This is one of the few cases in the literature where neonatal symptomatology led to the diagnosis of undiagnosed maternal hyperparathyroidism. Early detection and appropriate management of neonatal hypocalcemia could eliminate serious maternal and fetal morbidity.

Osteitis fibrosa cystica mimicking bone tumor, a case report.

BACKGROUND: We report a case of osteitis fibrosa cystica, a rare benign resorptive bone lesion caused by hyperparathyroidism, that presented on imaging as an aggressive bone tumor. CASE PRESENTATION: The patient is a 51-year-old male complaining of severe sustained pain of the right hip region. Imaging studies were suspicious for a malignant tumor of the right iliac bone. Biopsy under CT guidance was performed and showed remodeled bone trabeculae with numerous osteoclasts, excluding bone tumor and raising the possibility of osteitis fibrosa cystica. Complementary tests disclosed elevated blood level of parathyroid hormone and a partially cystic enlarged left inferior parathyroid gland consistent with adenoma. After parathyroidectomy, the clinical symptoms were relieved and the radiological findings were significantly improved, which confirmed the diagnosis. CONCLUSIONS: Metabolic diseases-associated bone lesions should always be considered in the differential diagnosis of bone tumors, to avoid unnecessary surgeries and treatments.